Rôle of Thrombin in Prothrombin Activation^[*]

Summary

The partial thromboplastin time and purified thrombin were used to demonstrate the procoagulant power of thrombin. Only 0.007 μg of thrombin could be detected in prothrombin activation. Traces of thrombin and autoprothrombin C can fully account for the generation of procoagulant activity in the thromboplastin generation test. Inactivation of these two activities by antithrombin explains the disappearance of the procoagulant power in that test, so that there now remains no valid demonstration of the existence of plasma thromboplastin or of anti-plasma thromboplastin.

^*) This investigation was supported by a research grant HE 03424-07 from the National Heart Institute, National Institutes of Health, U. S. Public Health Service. Heinz Schröer was the recipient of a Fulbright Travel Grant. Dieter Heene was the recipient of a grant from the German Academic Student Exchange Service.

• References

• 1 Astrup T. Autocatalysis and blood coagulation. Nature 144: 76 1939;
• 2 Astrup T. Blutgerinnung und Autokatalyse. Enzymologia 9: 337 1941;
• 3 Astrup T. The autocatalytic reaction in blood coagulation. Dan. med. Bull. p. 159 (1957)
• 4 Murray M, Johnson S. A, Seegers W. H. Relationship of certain antihistamine drugs to the activation of purified prothrombin. Amer. J. Physiol. 178: 10 1954;
• 5 Seegers W. H. Nature of the blood coagulation mechanisms. Thrombosis and Embolism. I. Internat. Conference, Basel, p. 31, 1954
• 6 Murray M, Johnson S. A, Seegers W. H. Activation of purified prothrombin in association with synthetic organic compounds and platelet extract. Science 119: 293 1954;
• 7 Seegers W. H, Levine W. G, Johnson S. A. Inhibition of prothrombin activation with dextran. J. appl. Physiol. 7: 617 1955;
• 8 Deutsch E, Johnson S. A, Seegers W. H. Differentiation of certain platelet factors related to blood coagulation. Circulat. Res. 3: 110 1955;
• 9 Seegers W. H. Coagulation of the blood. In: Advances in Enzymology and Related Subjects of Biochemistry 16: 23 1955;
• 10 Penner J. A, Seegers W. H. Activation of prothrombin. Amer. J. Physiol. 186: 343 1956;
• 11 Seegers W. H, Landaburu R. H. Esterase and clotting activity derived from purified prothrombin. Amer. J. Physiol. 191: 167 1957;
• 12 Landaburu R. H, Seegers W. H. Activation of prothrombin. Amer. J. Physiol. 193: 169 1958;
• 13 Seegers W. H, Marciniah E. Inhibition of autoprothrombin C activity with plasma. Nature 193: 1188 1962;
• 14 Seegers W. H, Cole E. R, Aoki N. Function of Ac-globulin and lipid in blood clotting. Canad. J. Biochem. 41: 2441 1963;
• 15 Marciniak E, Seegers W. H. Autoprothrombin C: A second enzyme from prothrombin. Canad. J. Biochem. 40: 597 1962;
• 16 Seegers W. H, Levine W. G, Shepard R. S. Further studies on the purification of thrombin. Canad. J. Biochem. 36: 603 1958;
• 17 Gole R. E, Marciniak E, Seegers W. H. Procedures for the quantitative determination of autoprothrombin C. Thrombos. Diathes. haemorrh. (Stuttg.) 8: 434 1962;
• 18 Stein H. B, Abrahams O. L. The mechanism of the thromboplastin generation test with reference to the role of thrombin. Proceedings of the Seventh International Congress of the International Society of Hematology, (Rome) Rome: Pensiero Scientifico, 1960
• 19 Connor W. E, Warner E. D, Garter J. R. A labile serum factor clotting defect: Its demonstration by the thromboplastin generation test and its clinical significance. J. clin. Invest. 40: 13 1961;
• 20 Seegers W. H, Cole E. R, Harmison C. R, Monkhouse F. C. Neutralization of autoprothrombin C activity with antithrombin. Canad. J. Biochem. 42: 359 1964;
• 21 Biggs R, Douglas A. S, Macfarlane R. G. The formation of thromboplastin in human blood. J. Physiol. (Lond.) 119: 89 1953;
• 22 Macfarlane R. G. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature (Lond.) 202: 498 1964;